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www.elsevier.es/ai
RESEARCH LETTER
Hodgkin’s lymphoma and late onset egg
allergy: is there a causal relationship?
To the Editor:
Hen’s egg is responsible for one of the most frequent
food allergies in childhood. About two-thirds of children will
outgrow their egg allergy by early school age (1). The persistence of egg allergy or its late onset has usually a less
favourable prognosis.
Hen’s egg is composed by a non-allergic shell (10% of
the egg), egg white (60%) and egg yolk (30%). Egg white
is 10% protein and 88% water, being more allergenic than
egg yolk. The former contains more than 20 proteins, four
of them being major allergens. The most prevalent protein is ovalbumin (Gal d 2, 55%), which is thermolabile. On
the other hand, ovomucoid (Gal d 1, 11%), ovotranferrin or
conalbumin (Gal d 3, 12%) and lysozyme (Gal d 4, 3%) are
heat-stable. Alpha-livetin or chicken serum albumin (Gal d
5) is the major allergen in egg yolk, being implicated in the
bird-egg syndrome.1
Food tolerance mechanisms are not completely understood but there are several known factors that can affect
it.2 It is postulated that a failure in oral tolerance induction
or a breakdown in previously acquired tolerance results in
food hypersensitivity. The latter is responsible for late onset
food allergy cases but it is not always possible to explain why
and how it happens.
We present a case of a female teenager who referred
recurrent oral allergy syndrome (OAS) since she was eleven,
within 2 months after Hodgkin’s lymphoma (mixed cellularity type, stage 3B) diagnosis and chemotherapy beginning
(with BEACOPP chemotherapy regimen: doxorubicin,
bleomycin, vincristine, cyclophosphamide, etoposide and
prednisone). After 6 months of chemotherapy, Hodgkin’s
lymphoma was in remission. She did not perform radiation
therapy.
At the age of 14 she began recurrent eyelid angiooedema, with no specific trigger. After an episode of glottis
oedema related to croissant ingestion, she decided to avoid
cakes and pastry. Besides that, she maintained recurrent
angio-oedema and she was referred to our allergy department in November of 2007, at 17 years. She had always
tolerated egg and egg containing foods until the age of 11
and she has never lost boiled egg tolerance. There was no
personal history of food allergy. She had no recent or past
history of birds or egg proteins exposition. Her personal history included pollinic rhinoconjuntivitis since she was 14.
She denied a clinical history of atopic eczema, asthma,
drug allergy or insect bite allergy. She also denied any regular medication (namely acid suppression treatment) besides
chemotherapy until she was 17.
The immunoallergic study revealed normal cell counts,
serum immunoglobulins, complement fractions, immunoelectrophoresis, lung function and chest X-ray. The study
of autoimmunity, celiac disease and viral serologies were
all negatives. The paranasal sinus X-ray showed maxillary
sinusitis. Skin prick tests (prick method) were performed
with a battery of common aeroallergens (ALK Abelló, Madrid,
Spain), epithelia (ALK Abelló, Madrid, Spain), food commercial extracts (Leti, Madrid, Spain) and skin prick tests
(prick-prick method) with fresh egg (raw and boiled), as well
as serum level of total and specific IgE. Table 1 presents
cutaneous and serum specific IgE reactivities.
Both clinical history and presented results are suggestive of a late onset egg allergy, soon after Hodgkin’s
lymphoma diagnosis and chemotherapy began. We have recommended eviction of foods containing raw egg; precaution
in the administration of egg-containing vaccines and she
was prescribed with a written treatment plan for reactions to unintentional exposure, including self-injectable
epinephrine.
Since then, she has had no more angio-oedema episodes.
She has grass pollen induced rhinoconjunctivitis and sinusitis
controlled under nasal corticosteroids and oral antihistamines on demand. Periodically, clinical and laboratorial
assessment has been made in order to look for an eventual
egg tolerance development.
We document a raw egg allergy case, namely to ovalbumin, a thermolabile protein responsible by the absence
of symptoms with boiled egg. This can be found as
an occult allergen in foods, namely in those incompletely cooked, which justifies recurrent angio-oedema
besides eviction of products in which egg presence was
undoubted.
Asero et al.3 also described an OAS in a 47-year-old
woman, after ingestion of egg-containing foods, besides
boiled egg tolerance.
Why did this patient, without previous food allergy,
lose egg tolerance at the age of 11? It has been suggested that the prevalence of food allergy is higher in
patients with gastrointestinal diseases,4 which can occur
0301-0546/$ – see front matter © 2010 SEICAP. Published by Elsevier España, S.L. All rights reserved.
doi:10.1016/j.aller.2010.06.009
Please cite this article in press as: Calado G, et al. Hodgkin’s lymphoma and late onset egg allergy: is there a causal
relationship? Allergol Immunopathol (Madr). 2011. doi:10.1016/j.aller.2010.06.009
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Table 1
Cutaneous and serum specific IgE results.
Extracts
Cutaneous specific IgE (mm)
Prick
Histamine
Grasses
10
10
Cat
Epithelia
Whole egg
Egg white
8
Negative
6
12
Egg yolk
3
Ovalbumin
Ovomucoid
Flours
Soybean
Cow’s milk:␣ and ␤-lactalbumin, casein
6
Negative
Negative
Negative
Negative
Serum specific IgE (KUI/L)
Prick-prick
Lolium perenne
21.9 (class 4)
1.3 (class 2)
Raw egg white: 16
Boiled egg white: negative
Raw egg yolk: 6
Boiled egg yolk: negative
0.9 (class 2)
<0.35
0.99 (class 2)
<0.35
Wheat <0.35
<0.35
Battery of common aeroallergens (ALK Abelló, Madrid, Spain), epithelia (ALK Abelló, Madrid, Spain), food commercial extracts (Leti,
Madrid, Spain) and fresh egg.
as a cause or a result of intestinal inflammation. Given
the closer temporal relationship between egg allergy symptoms and the diagnosis of Hodgkin’s lymphoma, this disease
and/or its treatment could have predisposed this patient
to egg sensitisation. This could happen by a mechanism
similar to that of Crohn’s disease, in which one of the
pathologic steps is the loss of oral tolerance to gut flora.5
Inflammation and infection can lead to intestinal epithelia tight-junctions disruption and, therefore, increase of
intestinal mucosa permeability with decrease of sensitisation threshold and loss of oral tolerance.6 This process could
also be induced by chemotherapy, since these drugs can
affect either the normal cells with high multiplication rates,
as is the case of bowel’s mucous membrane (enterotoxicity) or the gut flora, an immunomodulator of the immune
system. Constant microbial stimuli from the gut flora seem
to be required to keep a successful maturation of the gut
mucosal immune system. It has been reported that the lack
or inadequacy of such stimuli has resulted in a decreased
intestinal area, altered mucosal enzymes, defects in the
intestinal barrier function, reduced inflammatory responses,
a defective mucosal IgA system, and a deficient oral
tolerance.7
There is evidence that psychological stress, on its own,
can induce disruption of biological systems related to
inflammation through mechanisms potentially overlapping
with those altered by physical pollutants and toxicants.
It seems that stress influences neuroimmunoregulation
and oxidative stress pathways, which could modulate
hypersensitivity response. Some studies in mice models
proved that physical and psychological stress can induce
intestinal sensitisation to luminal antigens and oral tolerance disruption by inducing alterations in colonocyte
differentiation and decreased expression of RNAm encoding
tight junction proteins, with a consequent increase in
paracellular permeability and excessive uptake of luminal
material.8,9 Stress is also associated to gut flora changes,
with the possible consequences already discussed above.
Unsel et al.10 had reported a clinical case of egg allergy
onset at the age of 53, in a previous healthy woman,
after her 21-year-old daughter had died from a brain
tumour.
Thus, bowel mucous membrane can have two opposite roles in food allergy: a protecting role as an efficient
first-line protection against food allergy, conducing to oral
tolerance under physiological conditions; on the other hand,
it can be responsible either by the absence of tolerance gain
or by the lost of previously acquired tolerance, as probably
happened in this case.
This case report has some particularities, namely the
late onset egg allergy coincident with Hodgkin’s lymphoma
diagnosis and its persistence. We hypothesise that, in this
patient, the initial sensitisation to egg occurred through gut
mucosa as a consequence of Hodgkin’s lymphoma and/or
chemotherapy used in its treatment.
References
1. Tey D, Heine RG. Egg allergy in childhood: an update. Curr Opin
Allergy Clin Immunol. 2009;9:244—50.
2. Cochrane S, Beyer K, Clausen M, Wjst M, Hiller R, Nicoletti C,
et al. Factors influencing the incidence and prevalence of food
allergy. Allergy. 2009;64:1246—55.
3. Asero R, Mistrello G, Roncarolo D. Unusual egg allergy in an
adult. Allergy. 1999;54:1328—36.
4. Bischoff SC, Hermann A, Manns MP. Prevalence of adverse reactions to food in patients with gastrointestinal disease. Allergy.
1996;51:811—8.
5. James SP. Prototypic disorders of gastrointestinal mucosal
immune function: Celiac disease and Crohn’s disease. J Allergy
Clin Immunol. 2005;115:25—30.
6. Heyman M, Desjeux JF. Cytokine-induced alteration of the
epithelial barrier to food antigens in disease. Ann N Y Acad
Sci. 2000;915:304—11.
7. Kalliomäki M, Isolauri E. Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol. 2003;3:15—20.
Please cite this article in press as: Calado G, et al. Hodgkin’s lymphoma and late onset egg allergy: is there a causal
relationship? Allergol Immunopathol (Madr). 2011. doi:10.1016/j.aller.2010.06.009
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8. Yang PC, Jury J, Söderholm JD, Sherman PM, McKay DM, Perdue
MH. Chronic psychological stress in rats induces intestinal sensitization to luminal antigens. Am J Pathol. 2006;168:104—14.
9. Demaude J, Salvador-Cartier C, Fioramonti J, Ferrier L, Bueno
L. Phenotypic changes in colonocytes following acute stress
or activation of mast cells in mice: implications for delayed
epithelial barrier dysfunction. Gut. 2006;55:655—61.
10. Unsel M, Sin AZ, Ardeniz O, Erdem N, Ersoy R, Gulbahar O,
et al. New onset egg allergy in an adult. J Investig Allergol Clin
Immunol. 2007;17:55—8.
3
G. Calado a,∗ , D. Machado a , C. Ribeiro a , G. Loureiro a , B.
Tavares a , C. Pereira a , R. Cunha b , C. Chieira a
a
Immunoallergology Department, Coimbra University
Hospital, Coimbra, Portugal
b
Immunology sector of Clinical Pathology Department,
Coimbra University Hospital, Coimbra, Portugal
∗
Corresponding author.
E-mail address: [email protected] (G. Calado).
Please cite this article in press as: Calado G, et al. Hodgkin’s lymphoma and late onset egg allergy: is there a causal
relationship? Allergol Immunopathol (Madr). 2011. doi:10.1016/j.aller.2010.06.009